Chromosome segregation is a fundamental aspect of cell proliferation and appears to be altered in many cancers. The centromere is the central element of this process in which it plays a dual role as effector of chromosome movement and as regulator of mitotic progression. In most organisms centromeres are embedded in long stretches of repetitive DNA, are determined epigenetically, and consist of two distinct chromatin domains.
The first domain specifies kinetochore assembly and is built on a distinct type of nucleosome in which histone H3 substitutes for the centromere-specific histone CENP-A. The second domain is made of heterochromatin and is essential for sister chromatid cohesion that is mediated by a multiprotein complex called cohesin. This project aims to dissect the molecular mechanisms of centromere specification and function in the context of chromosome dynamics. We wish to identify novel factors (proteins, RNAs, histone modifications) that regulate the association of cohesin and CENP-A with chromatin both temporally (at different stages of the cell cycle) and spatially (at different chromosomal regions). Xenopus laevis egg cell-free extracts and mammalian tissue culture cells will be used as experimental systems in our studies.
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